What is the dosage and usage of Cyproheptadine for treating allergic reactions and stimulating appetite?

Cyproheptadine Dosage and Usage

Cyproheptadine is dosed at 4 mg three times daily in adults (maximum 32 mg/day) and 2 mg (0.25 mg/kg/day) two to three times daily in children aged 2-6 years for allergic symptoms, with critical emergency dosing of 12 mg initially followed by 2 mg every 2 hours for severe serotonin syndrome. 1, 2

Standard Dosing for Allergic Reactions

Adult Dosing

• Initial dose: 4 mg orally three times daily 1, 2
• Therapeutic range: 4-20 mg daily, with most patients requiring 12-16 mg daily 2
• Maximum dose: 32 mg/day (not to exceed 0.5 mg/kg/day) 2
• Adjust according to patient size and response 2

Pediatric Dosing (Ages 2-6 years)

• Standard dose: 2 mg (½ tablet) two to three times daily 2
• Calculate based on 0.25 mg/kg/day or 8 mg/m² body surface area 2
• Maximum: 12 mg/day 2
• Available as 2 mg/5 mL syrup for easier administration 3, 1

Pediatric Dosing (Ages 7-14 years)

• Standard dose: 4 mg (1 tablet) two to three times daily 2
• Maximum: 16 mg/day 2
• Adjust based on patient size and response 2

Critical Emergency Indication: Severe Serotonin Syndrome

Cyproheptadine is the preferred antidote for serotonin syndrome, which carries an 11% mortality rate with complications including rhabdomyolysis, metabolic acidosis, renal failure, and seizures. 1

Adult Emergency Dosing

• Initial: 12 mg orally immediately 1
• Continuation: 2 mg every 2 hours for ongoing symptoms 1
• Maintenance: 8 mg every 6 hours once stabilized 1

Pediatric Emergency Dosing

• Dose: 0.25 mg/kg per day 1, 4
• Tablets can be crushed and administered via nasogastric tube if needed (no parenteral form available) 1, 4

Critical Monitoring Requirements

• ICU-level monitoring with preparation for rapid deterioration 1
• Avoid indirect sympathomimetics like dopamine; use direct-acting agents (phenylephrine, norepinephrine) instead 1
• If intubation required, use non-depolarizing paralytic agents; avoid succinylcholine due to hyperkalemia and rhabdomyolysis risks 1

Appetite Stimulation (Off-Label)

Pediatric Cancer-Related Cachexia

• Effective dose range: 4-8 mg daily 5
• Average weight gain: 2.6 kg over 4 weeks in responders 5
• Response rate: 76% (50/66 patients) 5
• Mean weight-for-age z-score improvement: 0.35 (P=0.001) 5

General Appetite Stimulation

• Mean effective dose: 4.85 mg/day (0.14 mg/kg/day) 6
• Higher body mass index predicts better response (1 unit BMI increase = 1.5-fold increased odds of improvement, P=0.01) 6
• Lower body weight associated with reduced response 6

Mast Cell Activation Syndrome (MCAS)

Cyproheptadine provides dual benefit through H1-antihistamine and antiserotonergic properties, specifically targeting gastrointestinal symptoms including diarrhea, nausea, and abdominal cramping. 3, 1

• Mechanism: Blocks both histamine H1 receptors and serotonin receptors for broader symptom control 1
• Particularly effective for gastrointestinal manifestations compared to standard antihistamines 3

Functional Gastrointestinal Disorders (Off-Label)

Efficacy by Condition

• Functional abdominal pain/dyspepsia: 73% complete improvement 6
• Irritable bowel syndrome: 100% improvement (10/10 patients) 6
• Cyclic vomiting syndrome: 75% improvement (6/8 patients) 6
• Abdominal migraine: 72% improvement (13/18 patients) 6
• Retching after Nissen fundoplication: 86% response rate 7

Dosing for Dyspeptic Symptoms

• Mean effective dose: 4.85-5.34 mg/day 6
• Better response in younger children and females (P=0.04 and 0.03) 6, 7
• Early vomiting (within 1 hour of meals) responds better than late vomiting (P=0.03) 7

Critical Safety Considerations

High-Risk Populations

Elderly patients face significant cognitive decline risk due to anticholinergic effects, with impaired driving ability and potential cardiovascular concerns. 3, 1

• Sedation incidence: 9-11% overall, but higher in elderly 1
• Cognitive impairment may occur without subjective awareness 1
• Avoid in patients prone to cardiovascular events 3

Common Adverse Effects

• Drowsiness: Most frequent (13-16% in pediatric studies) 8, 5, 6, 7
• Weight gain: 10-15% of patients 6, 7
• Irritability and behavioral changes: 6% 7
• Anticholinergic effects: dry mouth, dry eyes, constipation, urinary retention 1

Serious but Rare Complications

• Hepatotoxicity: Estimated frequency 0.27-1.4 per 1000 patients 8
• Very rare cases of liver failure reported 8
• 15 hepatic complications reported in French pharmacovigilance database (86.7% adults, 13.3% children) 8
• Monitor liver function, especially with prolonged use 8

Contraindications and Precautions

• Avoid concomitant use with alcohol and other CNS-active substances (enhances performance impairment) 1
• Risk of narrow-angle glaucoma due to anticholinergic effects 1
• Use caution with cerebrovascular/cardiovascular disease, hyperthyroidism, bladder neck obstruction 3
• Only 2 patients (2.5%) discontinued therapy due to side effects in pediatric studies 7

Drug Interactions

• Avoid with MAOIs, SSRIs, other triptans, ergot-type medications 3
• Enhanced sedation with other antihistamines and CNS depressants 1

Advantages Over Second-Generation Antihistamines

Cyproheptadine provides superior control of rhinorrhea compared to second-generation antihistamines due to its anticholinergic effects, though this comes at the cost of increased sedation. 1

• First-generation properties allow better mucus control 1
• Antiserotonergic activity provides additional therapeutic benefit for gastrointestinal symptoms 3, 1
• More effective for conditions requiring both antihistamine and anticholinergic effects 1